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8. Pharmacologic Approaches to Glycemic
Treatment: Standards of Medical Care in Diabetes
—2018

American Diabetes Association

2
Diabetes Care 2018 Jan; 41(Supplement 1): S73-S85.
https://doi.org/10.2337/dc18-S008

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ARTICLE FIGURES & TABLES

Figures % Tables

Figure 8.1 Download !gure | Open in new tab | Download powerpoint

Antihyperglycemic therapy in type 2 diabetes: general recommendations. *If patient does not
tolerate or has contraindications to metformin, consider agents from another class in Table 8.1.
#GLP-1 receptor agonists and DPP-4 inhibitors should not be prescribed in combination. If a
patient with ASCVD is not yet on an agent with evidence of cardiovascular risk reduction,
consider adding.

Figure 8.2 Download !gure | Open in new tab | Download powerpoint

Combination injectable therapy for type 2 diabetes. FBG, fasting blood glucose; hypo,
hypoglycemia. Adapted with permission from Inzucchi et al. (31).

Tables & Figures

Table 8.1

Drug-speci!c and patient factors to consider when selecting antihyperglycemic treatment in

adults with type 2 diabetes

*See ref. 31 for description of e"cacy. †FDA approved for CVD bene!t. CVD, cardiovascular
disease; DKA, diabetic ketoacidosis; DKD, diabetic kidney disease; NASH, nonalcoholic
steatohepatitis; RAs, receptor agonists; SQ, subcutaneous; T2DM, type 2 diabetes.

Table 8.2

Pharmacology of available glucose-lowering agents in the U.S. for the treatment of type 2
diabetes

Class Compound(s) Cellular Primary Renal dosing

mechanism(s) physiological recommendations
action(s) (63–66)*

Biguanides • Metformin Activates AMP ↓ Hepatic glucose No dose

kinase (? production adjustment if
other) eGFR >45;

do not initiate
OR assess
risk/bene!t if
currently on
metformin if
eGFR 30–45;

discontinue if
eGFR <30

Sulfonylureas (2nd • Glyburide Closes KATP ↑ Insulin secretion • Avoid use in

generation) channels on β- patients with renal
cell plasma impairment
membranes
• Glipizide • Initiate
conservatively at
2.5 mg daily to
avoid hypoglycemia

• Glimepiride • Initiate
conservatively at 1
mg daily to avoid
hypoglycemia

Meglitinides • Repaglinide Closes KATP ↑ Insulin secretion • Initiate

(glinides) channels on β- conservatively at
cell plasma 0.5 mg with meals if
membranes eGFR <30

• Nateglinide • Initiate
conservatively at 60
mg with meals if
eGFR <30

Thiazolidinediones • Pioglitazone Activates the ↑ Insulin sensitivity • No dose

nuclear adjustment required
transcription
• factor PPAR-γ • No dose
Rosiglitazone§§ adjustment required

α-Glucosidase • Acarbose Inhibits Slows intestinal • Avoid if eGFR <30

inhibitors intestinal α- carbohydrate
• Miglitol glucosidase digestion/absorption • Avoid if eGFR <25

DPP-4 inhibitors • Sitagliptin Inhibits DPP-4 Insulin 100 mg daily if

activity, secretion eGFR >50;
increasing (glucose
postprandial dependent); 50 mg daily if
incretin (GLP- eGFR 30–50;
1, GIP) Glucagon
concentrations secretion 25 mg daily if
(glucose eGFR <30
dependent)

• Saxagliptin 5 mg daily if
eGFR >50;

2.5 mg daily if
eGFR ≤50

• Linagliptin • No dose
adjustment required

• Alogliptin 25 mg daily if
eGFR >60;

12.5 mg daily if
eGFR 30–60;

6.25 mg daily if
eGFR <30

Bile acid • Colesevelam Binds bile ? Hepatic • No specific dose

sequestrants acids in glucose adjustment
intestinal tract, production; recommended by
increasing manufacturer
hepatic bile ? Incretin
acid levels
production

Dopamine-2 • Activates Modulates • No specific dose

agonists Bromocriptine dopaminergic hypothalamic adjustment
(quick receptors regulation of recommended by
release)§§ metabolism; manufacturer

Insulin
sensitivity

SGLT2 inhibitors • Canagliflozin Inhibits SGLT2 Blocks glucose No dose

in the proximal reabsorption by the adjustment
nephron kidney, increasing required if
glucosuria eGFR ≥60;

100 mg daily if
eGFR 45–59;

avoid use and

discontinue in
patients with
eGFR
persistently
<45

• Dapagliflozin Avoid initiating

if eGFR <60;

not
recommended
with eGFR 30–
60;

contraindicated
with eGFR <30

• • Contraindicated
Empagliflozin with eGFR <30

GLP-1 receptor • Exenatide Activates Insulin • Not recommended

agonists GLP-1 secretion with eGFR <30
receptors (glucose
• Exenatide dependent) • Not recommended
extended with eGFR <30
release Glucagon
secretion
• Liraglutide (glucose • No specific dose
dependent); adjustment
recommended by
Slows gastric the manufacturer;
emptying; limited experience
in patients with
Satiety severe renal
impairment

• Albiglutide • No dose
adjustment required
for eGFR 15–89 per
manufacturer;
limited experience
in patients with
severe renal
impairment

• Lixisenatide No dose
adjustment
required for
eGFR 60–89;

no dose
adjustment
required for
eGFR 30–59,
but patients
should be
monitored for
adverse e$ects
and changes in
kidney
function;

clinical
experience is
limited with
eGFR 15–29;
patients should
be monitored
for adverse
e$ects and
changes in
kidney
function;

avoid if eGFR
<15

• Dulaglutide • No specific dose

adjustment
recommended by
the manufacturer;
limited experience
in patients with
severe renal
impairment

Amylin mimetics • Pramlintide§§ Activates Glucagon • No specific dose

amylin secretion; adjustment
receptors recommended by
Slows gastric manufacturer
emptying;

Satiety

Insulins • Rapid-acting Activates Glucose • Lower insulin

analogs insulin disposal; doses required with
receptors a decrease in eGFR;
Lispro Hepatic titrate per clinical
glucose response
Aspart production;

Suppresses
Glulisine
ketogenesis

Inhaled insulin

• Short-acting
analogs

Human
Regular

•
Intermediate-
acting
analogs

Human NPH

• Basal insulin
analogs

Glargine

Detemir

Degludec

• Premixed
insulin
products

NPH/Regular
70/30

70/30 aspart
mix

75/25 lispro
mix

50/50 lispro
mix

*eGFR is given in mL/min/1.73 m2.

↵§ Not licensed in Europe for type 2 diabetes.

GIP, glucose-dependent insulinotropic peptide; PPAR-γ, peroxisome proliferator–activated

receptor γ.

Table 8.3

Median monthly cost of maximum approved daily dose of noninsulin glucose-lowering agents
in the U.S.

Class Compound(s) Dosage Median Median Maximum

strength/product AWP NADAC approved
(if applicable) (min, (min, daily dose**
max)†† max)††

Biguanides • Metformin 500 mg (IR) $84 ($4, $2 2,000 mg

$93)

850 mg (IR) $108 $3 2,550 mg

($6,
$109)

1,000 mg (IR) $87 ($4, $2 2,000 mg

$88)

500 mg (ER) $89 $5 ($5, 2,000 mg

($82, $3,630)
$6,671)

750 mg (ER) $72 $5 1,500 mg

($65,
$92)

1,000 mg (ER) $1,028 $539 2,000 mg

($1,028, ($539,
$7,214) $5,189)

Sulfonylureas (2nd • Glyburide 5 mg $93 $17 20 mg

generation) ($63,
$103)

6 mg (micronized) $50 $12 12 mg

($48, (micronized)
$71)

• Glipizide 10 mg (IR) $75 $4 40 mg (IR)

($67,
$97)

10 mg (XL) $48 $16 20 mg (XL)

• Glimepiride 4 mg $71 $7 8 mg
($71,
$198)

Meglitinides • Repaglinide 2 mg $659 $40 16 mg

(glinides) ($122,
$673)

• Nateglinide 120 mg $155 $56 360 mg

Thiazolidinediones • Pioglitazone 45 mg $348 $5 45 mg

($283,
$349)

• 4 mg $387 $314 8 mg
Rosiglitazone

α-Glucosidase • Acarbose 100 mg $104 $25 300 mg

inhibitors ($104,
$106)

• Miglitol 100 mg $241 N/A†††† 300 mg

DPP-4 inhibitors • Sitagliptin 100 mg $477 $382 100 mg

• Saxagliptin 5 mg $462 $370 5 mg

• Linagliptin 5 mg $457 $367 5 mg

• Alogliptin 25 mg $449 $357 25 mg

Bile acid • Colesevelam 625 mg tabs $713 $570 3.75 g

sequestrants
1.875 g $1,426 $572 3.75 g
suspension

Dopamine-2 • 0.8 mg $784 $629 4.8 mg

agonists Bromocriptine

SGLT2 inhibitors • Canagliflozin 300 mg $512 $411 300 mg

• Dapagliflozin 10 mg $517 $413 10 mg

• 25 mg $517 $415 25 mg
Empagliflozin

GLP-1 receptor • Exenatide 10 μg pen $802 $642 20 μg

agonists
• Lixisenatide 20 μg pen $669 N/A†††† 20 μg

• Liraglutide 18 mg/3 mL pen $968 $775 1.8 mg

• Exenatide 2 mg powder for $747 $600 2 mg****

(extended suspension or
release) pen

• Albiglutide 50 mg pen $626 $500 50 mg****

• Dulaglutide 1.5/0.5 mL pen $811 $648 1.5 mg****

Amylin mimetics • Pramlintide 120 μg pen $2,336 N/A†††† 120

μg/injection††††††

ER and XL, extended release; IR, immediate release.

†Calculated for 30-day supply (AWP or NADAC unit price × number of doses required to provide
maximum approved daily dose × 30 days); median AWP or NADAC listed alone when only one
product and/or price.

*Utilized to calculate median AWP and NADAC (min, max); generic prices used, if available
commercially.

↵†† Not applicable; data not available.

↵** Administered once weekly.

↵††† AWP and NADAC calculated based on 120 μg three times daily.

Table 8.4

Median cost of insulin products in the U.S. calculated as AWP (39) and NADAC (40) per 1,000
units of speci!ed dosage form/product

Insulins Compounds Dosage Median Median

form/product AWP NADAC
(min, (min,
max)** max)**

Rapid-acting analogs • Lispro U-100 vial; $330 $264

U-100 3 mL $408 $326

cartridges;

U-100 prefilled pen; $424 $339

U-200 prefilled pen

• Aspart U-100 vial; $331 $265

U-100 3 mL $410 $330

cartridges;

U-100 prefilled pen $426 $341

• Glulisine U-100 vial; $306 $245

U-100 prefilled pen $394 $315

• Inhaled insulin Inhalation cartridges $725 N/A††

($544,
$911)

Short-acting analogs • Human Regular U-100 vial $165 $135

($165, ($135,
$178) $145)

Intermediate-acting • Human NPH U-100 vial; $165 $135

analogs ($165, ($135,
$178) $145)

U-100 prefilled pen $377 $305

Concentrated Human • U-500 Human U-500 vial; $178 $143

Regular insulin Regular insulin
U-500 prefilled pen $230 $184

Basal analogs • Glargine U-100 vial; U-100 $298 $239

prefilled pen; U-300 ($239,
prefilled pen $241)

• Glargine biosimilar U-100 prefilled pen $253 $203

• Detemir U-100 vial; U-100 $323 $259

prefilled pen

• Degludec U-100 prefilled pen; $355 $285

U-200 prefilled pen

Premixed insulin • NPH/Regular 70/30 U-100 vial; $165 $134

products ($165, ($134,
$178) $146)

U-100 prefilled pen $377 $305

• Lispro 50/50 U-100 vial; $342 $278

U-100 prefilled pen $424 $339

• Lispro 75/25 U-100 vial; $342 $273

U-100 prefilled pen $424 $340

• Aspart 70/30 U-100 vial; $343 $275

U-100 prefilled pen $426 $341

Premixed insulin/GLP-1 • 100/3.6 prefilled pen $763 N/A††

receptor agonist Degludec/Liraglutide
products
• 100/33 prefilled pen $508 $404
Glargine/Lixisenatide

*AWP or NADAC calculated as in Table 8.3

8.3; median listed alone when only one product and/or
price.

†Not applicable; data not available.

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